Pericyte Depletion Results in Hypoxia-Associated Epithelial-to-Mesenchymal Transition and Metastasis Mediated by Met Signaling Pathway

The functional role of pericytes in cancer progression remains unknown. Clinical studies suggest that low numbers of vessel-associated pericytes correlated with a drop in overall survival of patients with invasive breast cancer. Using genetic mouse models or pharmacological inhibitors, pericyte depl...

Full description

Bibliographic Details
Main Authors: Cooke, Vesselina G., LeBleu, Valerie Sandra, Keskin, Doruk, Khan, Zainab, O’Connell, Joyce T., Teng, Yingqi, Duncan, Michael B., Xie, Liang, Maeda, Genta, Vong, Sylvia, Sugimoto, Hikaru, Rocha, Rafael M., Damascena, Aline, Brentani, Ricardo R., Kalluri, Raghu
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: Elsevier B.V. 2014
Online Access:http://hdl.handle.net/1721.1/91948
Description
Summary:The functional role of pericytes in cancer progression remains unknown. Clinical studies suggest that low numbers of vessel-associated pericytes correlated with a drop in overall survival of patients with invasive breast cancer. Using genetic mouse models or pharmacological inhibitors, pericyte depletion suppressed tumor growth but enhanced metastasis. Pericyte depletion was further associated with increased hypoxia, epithelial-to-mesenchymal transition (EMT), and Met receptor activation. Silencing of Twist or use of a Met inhibitor suppressed hypoxia and EMT/Met-driven metastasis. In addition, poor pericyte coverage coupled with high Met expression in cancer cells speculates the worst prognosis for patients with invasive breast cancer. Collectively, our study suggests that pericytes within the primary tumor microenvironment likely serve as important gatekeepers against cancer progression and metastasis.